Beta cell endoplasmic reticulum stress drives diabetes in the KINGS mouse without causing mass beta cell loss.
Diabet Med
; 39(12): e14962, 2022 12.
Article
in En
| MEDLINE
| ID: mdl-36151994
ABSTRACT
AIMS:
Beta cell endoplasmic reticulum (ER) stress can cause cellular death and dysfunction and has been implicated in the pathogenesis of diabetes. Animal models of beta cell ER stress are critical in further understanding this and for testing novel diabetes therapeutics. The KINGS mouse is a model of beta cell ER stress driven by a heterozygous mutation in Ins2. In this study, we investigated how beta cell ER stress in the KINGS mouse drives diabetes.METHODS:
We investigated whether the unfolded protein response (UPR) was activated in islets isolated from male and female KINGS mice and whether this impacted beta cell mass and turnover.RESULTS:
Whilst the UPR was up-regulated in KINGS islets, with increased protein expression of markers of all three UPR arms, this was not associated with a mass loss of beta cells; beta cell apoptosis rates did not increase until after the development of overt diabetes, and did not lead to substantial changes in beta cell mass.CONCLUSION:
We propose that the KINGS mouse represents a model where beta cell maladaptive UPR signalling drives diabetes development without causing mass beta cell loss.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Diabetes Mellitus
/
Insulin-Secreting Cells
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Diabet Med
Journal subject:
ENDOCRINOLOGIA
Year:
2022
Document type:
Article
Affiliation country:
United kingdom